DOCSLIB.ORG

Organic Acidemias/Acidurias Precision Panel Overview

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Organic Acidemias/Acidurias Precision Panel Overview Organic Acidemias/Acidurias Precision Panel Overview Organic Acidemias/Acidurias (Organic Acid Disorders, OADs) are an important group of inherited metabolic disorders that share a defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation. These enzymatic defects lead to an accumulation of organic acids in tissues and their subsequent excretion in urine. As patients age, the natural progression of organic acidemias lead to intellectual difficulties, increased risk for neurologic complications such as stroke-like episodes and cardiac complications among others. All organic acidurias are inherited in an autosomal recessive pattern. The Igenomix Organic Acidemias/Acidurias Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis of hyperammonemia and high anion gap metabolic acidosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved. Indications The Igenomix Organic Acidemias/Acidurias Precision Panel is indicated for those patients with a clinical suspicion or diagnosis an organic acidemia with or without the following manifestations: - Developmental delay - Mental retardation - Seizures - Lethargy - Coma - Hypotonia - Vomiting - Failure to thrive - Hepatomegaly - Respiratory distress - Cardiac dysfunction Clinical Utility The clinical utility of this panel is: 1 - The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient. - Early initiation of treatment with a multidisciplinary team in the form of nutritional therapy, correction of fluid and electrolyte imbalances, adequate cerebral perfusion. - Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance. - Improvement of delineation of genotype-phenotype correlation. Genes & Diseases % GENE GENE OMIM DISEASES INHERITANCE* HGMD** COVERAGE (20X) ABCD4 Methylmalonic Aciduria And Homocystinuria AR 100 8 of 8 ACAD8 Isobutyryl-CoA Dehydrogenase Deficiency AR 100 35 of 35 ACAD9 Acyl-CoA Dehydrogenase Family AR 100 62 of 62 ACADL Long Chain Acyl-CoA Dehydrogenase Deficiency - 100 1 of 1 ACADM Medium Chain Acyl-CoA Dehydrogenase Deficiency AR 99.98 181 of 181 ACADS Shot-Chain Acyl-coa Dehydrogenase Deficiency AR 100 84 of 84 ACADSB 2-Methylbutyryl-CoA Dehydrogenase Deficiency AR 100 21 of 21 ACADVL Very Long Chain Acyl-CoA Dehydrogenase Deficiency AR 100 329 of 329 Alpha-Methylacetoacetic Aciduria, Beta-Ketothiolase ACAT1 AR 100 116 of 116 Deficiency ACSF3 Combined Malonic And Methylmalonic Aciduria AR 100 27 of 27 ADK Hypermethioninemia Due To Adenosine Kinase Deficiency AR 100 15 of 16 Congenital Cataract-Hypertrophic Cardiomyopathy- AGK AR 99.98 33 of 33 Mitochondrial Myopathy Syndrome AGXT Primary Hyperoxaluria Type 1 AR 99.99 210 of 211 Hypermethioninemia With S-Adenosylhomocysteine AHCY AR 100 11 of 11 Hydrolase Deficiency ALDH4A1 Hyperprolinemia Type II AR 100 7 of 7 ALDH5A1 Succinic Semialdehyde Dehydrogenase Deficiency AR 95.41 65 of 69 ALDOB Hereditary Fructose Intolerance AR 100 61 of 65 AMN Imerslund-Grasbeck Syndrome AR 94.02 31 of 32 AMT Glycine Encephalopathy AR 99.98 94 of 96 ARG1 Argininemia AR 100 66 of 68 ASL Argininosuccinic Aciduria AR 100 170 of 170 ASPA Canavan Disease AR 99.56 93 of 94 ASS1 Classic Citrullinemia AR 100 150 of 153 Harel-Yoon Syndrome, Pontocerebellar Hypoplasia, ATAD3A AD,AR 90.98 6 of 8 Hypotonia, And Respiratory Insufficiency Syndrome Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear ATP5F1D AR 98.19 NA of NA Type 5 Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear ATP5F1E AR 100 NA of NA Type 3 Leber Optic Atrophy, Neuropathy, Ataxia, And Retinitis ATP6 Pigmentosa, Mitochondrial DNA-Associated Leigh Syndrome, MI na na Narp Syndrome ATP7B Wilson Disease AR 99.97 989 of 1000 ATPAF2 ATPase Deficiency Nuclear-Encoded AR 100 2 of 2 AUH 3-Methylglutaconic Aciduria Type I AR 99.99 11 of 11 BCKDHA Maple Syrup Urine Disease AR 98.41 96 of 97 BCKDHB Maple Syrup Urine Disease AR 99.99 122 of 123 Bjornstad Syndrome, Gracile Syndrome, Leigh Syndrome, BCS1L AR,MI 99.96 40 of 42 Mitochondrial Complex III Deficiency BTD Biotinidase Deficiency Multiple Carboxylase Deficiency AR 100 261 of 262 CAMKMT 2p21 Microdeletion Syndrome - 99.99 NA of NA Neonatal Severe Primary Hyperparathyroidism, Familial CASR AD,AR 100 445 of 446 Hypocalciuric Hypercalcemia CBS Classic Homocystinuria AR 99.98 192 of 194 CCN6 Progressive Pseudorheumatoid Arthropathy Of Childhood AR 100 NA of NA Methylmalonic Aciduria Due To Transcobalamin Receptor CD320 AR 89 2 of 2 Defect 2 Dent Disease, X-linked Recessive Hypophosphatemic Rickets, CLCN5 Nephrolithiasis With Renal Failure , Low Molecular Weight X,XR,G 99.39 NA of NA Proteinuria With Hypercalciuria And Nephrocalcinosis CLPB 3-Methylglutaconic Aciduria Type 7 AR 96 26 of 26 COA3 Mitochondrial Complex IV Deficiency AR,MI 100 2 of 2 Mitochondrial Complex IV Deficiency, Non-Progressive COA8 Predominantly Posterior Cavitating Leukoencephalopathy AR,MI 86.26 4 of 5 With Peripheral Neuropathy COX10 Leigh Syndrome, Mitochondrial Complex IV Deficiency AR,MI 100 13 of 13 COX14 Mitochondrial Complex IV Deficiency AR,MI 100 1 of 1 COX20 Mitochondrial Complex IV Deficiency AR,MI 99.88 5 of 5 COX6B1 Mitochondrial Complex IV Deficiency AR,MI 100 3 of 3 COX8A Mitochondrial Complex IV Deficiency AR,MI 100 1 of 1 CPS1 Carbamoyl Phosphate Synthetase I Deficiency AR 100 274 of 278 CPT2 Infantile Carnitine Palmitoyltransferase II AD,AR 99.99 116 of 116 CTH Cystathioninuria AR 100 8 of 8 Cystinosis Adult Nonnephropathic, Nephropathic Infantile CTNS AR 100 148 of 153 Cystinosis CUBN Megaloblastic Anemia AR 100 53 of 54 CYP27B1 Hypocalcemic Vitamin D-Dependent Rickets AR 98.45 80 of 80 CYP2R1 Hypocalcemic Vitamin D-Dependent Rickets AR 99.22 6 of 6 D2HGDH D-2-Hydroxyglutaric Aciduria AR 100 42 of 42 DBT Maple Syrup Urine Disease AR 100 73 of 75 DDB2 Xeroderma Pigmentosum Complementation Group E AR 100 17 of 17 Progressive External Ophthalmoplegia With Mitochondrial DGUOK AR 100 68 of 70 DNA Deletions 2-Aminoadipic 2-Oxoadipic Aciduria, Charcot-Marie-Tooth DHTKD1 AD,AR 99.94 25 of 25 Disease, Axonal Type 2q Dihydrolipoamide Dehydrogenase Deficiency, Pyruvate DLD AR 100 26 of 26 Dehydrogenase E3 Deficiency DMGDH Dimethylglycine Dehydrogenase Deficiency AR 99.77 2 of 2 3-Methylglutaconic Aciduria Type V, Dilated Cardiomyopathy DNAJC19 AR 100 6 of 6 With Ataxia EHHADH Fanconi Renotubular Syndrome AD 99.96 1 of 1 Cerebrooculofacioskeletal Syndrome, Xeroderma ERCC2 AR 100 102 of 102 Pigmentosum Complementation Group D Photosensitive Trichothiodystrophy, Xeroderma Pigmentosum ERCC3 AR 99.98 24 of 24 Complementation Group B Fanconi Anemia Complementation Group Q, Xeroderma ERCC4 Pigmentosum Complementation Group F, Cockayne AR 99.68 69 of 72 Syndrome Type 1 Cerebrooculofacioskeletal Syndrome, Xeroderma ERCC5 AR 99.94 58 of 58 Pigmentosum, Complementation Group G ETFA Multiple Acyl-CoA Dehydrogenase Deficiency AR 92.33 32 of 32 ETFB Multiple Acyl-CoA Dehydrogenase Deficiency AR 100 21 of 21 ETFDH Multiple Acyl-CoA Dehydrogenase Deficiency AR 100 221 of 222 ETHE1 Ethylmalonic Encephalopathy AR 100 32 of 33 FAH Tyrosinemia Type 1 AR 100 107 of 108 FARS2 Combined Oxidative Phosphorylation Deficiency AR 99.98 23 of 23 FH Fumarase Deficiency AD,AR 100 229 of 232 Lipid Storage Myopathy Due To Flavin Adenine Dinucleotide FLAD1 AR 97.13 13 of 14 Synthetase Deficiency FTCD Formiminotransferase Deficiency AR 99.83 17 of 17 GALE Galactose Epimerase Deficiency AR 100 29 of 29 GALT Classic Galactosemia AR 100 350 of 350 Cerebral Creatine Deficiency Syndrome, Fanconi Renotubular GATM AD,AR 99.98 21 of 21 Syndrome GCDH Glutaric Acidemia, Glutaryl-CoA Dehydrogenase Deficiency AR 88.74 254 of 254 GCLC Gamma-Glutamyl-Cysteine Synthetase Deficiency AR 99.97 7 of 7 GCSH Glycine Encephalopathy AR 93.52 1 of 1 Neurodevelopmental Disorder With Microcephaly, Cataracts, GEMIN4 AR 99 2 of 2 And Renal Abnormalities GIF Autosomal Recessive Intrinsic Factor Deficiency - 100 NA of NA GLDC Glycine Encephalopathy AR 98.69 359 of 367 GLYCTK D-glyceric Aciduria AR 100 6 of 6 GNMT Glycine N-Methyltransferase Deficiency AR 100 5 of 5 Hyperekplexia, Hereditary , Molybdenum Cofactor Deficiency, GPHN AD,AR 99.2 6 of 6 Complementation Group C 3 GRHPR Primary Hyperoxaluria Type 2 AR 88 51 of 51 GSS Glutathione Synthetase Deficiency AR 100 36 of 38 Central Areolar Choroidal Dystrophy, Cone-Rod Dystrophy, GUCY2D Leber Congenital Amaurosis Type I, Congenital Stationary AD,AR 99.98 248 of 248 Night Blindness HADH 3-Hydroxyacyl-CoA Dehydrogenase Deficiency AR 96.71 26 of 27 HAL Histidinemia - 100 9 of 9 HCFC1 Methylmalonic Acidemia And Homocysteinemia X,XR,G 99.81 NA of NA HGD Alkaptonuria AR 100 158 of 159 HIBCH 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency AR 96.47 27 of 27 HLCS Holocarboxylase Synthetase Deficiency AR 100 47 of 47 HMGCL 3-Hydroxy-3-Methylglutaric Aciduria AR 100 54 of 54 HMGCS2 3-Hydroxy-3-Methylglutaryl-CoA Synthase-2 Deficiency AR 100 37 of 37 Fanconi Renotubular Syndrome With Maturity-Onset Diabetes HNF4A Of The Young, Hnf1b-Related Autosomal Dominant AD 100 172 of 174 Tubulointerstitial Kidney Disease HOGA1 Primary Hyperoxaluria Type 3 AR 100 42 of 42 HPD Hawkinsinuria, Tyrosinemia Type III AD,AR 100 10 of 10 3-Methylglutaconic Aciduria Type VIII, Young-Onset Parkinson HTRA2 AD,AR 99.81 18 of 18 Disease
Load more

Recommended publications
  • Supplementary Materials
    DEPs in osteosarcoma cells comparing to osteoblastic cells Biological Process Protein Percentage of Hits metabolic process (GO:0008152) 29.3 29.3% cellular process (GO:0009987) 20.2 20.2% localization (GO:0051179) 9.4 9.4% biological regulation (GO:0065007) 8 8.0% developmental process (GO:0032502) 7.8 7.8% response to stimulus (GO:0050896) 5.6 5.6% cellular component organization (GO:0071840) 5.6 5.6% multicellular organismal process (GO:0032501) 4.4 4.4% immune system process (GO:0002376) 4.2 4.2% biological adhesion (GO:0022610) 2.7 2.7% apoptotic process (GO:0006915) 1.6 1.6% reproduction (GO:0000003) 0.8 0.8% locomotion (GO:0040011) 0.4 0.4% cell killing (GO:0001906) 0.1 0.1% 100.1% Genes 2179Hits 3870 biological adhesion apoptotic process … reproduction (GO:0000003) , 0.8% (GO:0022610) , 2.7% locomotion (GO:0040011) ,… immune system process cell killing (GO:0001906) , 0.1% (GO:0002376) , 4.2% multicellular organismal process (GO:0032501) , metabolic process 4.4% (GO:0008152) , 29.3% cellular component organization (GO:0071840) , 5.6% response to stimulus (GO:0050896), 5.6% developmental process (GO:0032502) , 7.8% biological regulation (GO:0065007) , 8.0% cellular process (GO:0009987) , 20.2% localization (GO:0051179) , 9.
    [Show full text]
  • Hyperammonemia in Review: Pathophysiology, Diagnosis, and Treatment
    Pediatr Nephrol DOI 10.1007/s00467-011-1838-5 EDUCATIONAL REVIEW Hyperammonemia in review: pathophysiology, diagnosis, and treatment Ari Auron & Patrick D. Brophy Received: 23 September 2010 /Revised: 9 January 2011 /Accepted: 12 January 2011 # IPNA 2011 Abstract Ammonia is an important source of nitrogen and is the breakdown and catabolism of dietary and bodily proteins, required for amino acid synthesis. It is also necessary for respectively. In healthy individuals, amino acids that are not normal acid-base balance. When present in high concentra- needed for protein synthesis are metabolized in various tions, ammonia is toxic. Endogenous ammonia intoxication chemical pathways, with the rest of the nitrogen waste being can occur when there is impaired capacity of the body to converted to urea. Ammonia is important for normal animal excrete nitrogenous waste, as seen with congenital enzymatic acid-base balance. During exercise, ammonia is produced in deficiencies. A variety of environmental causes and medica- skeletal muscle from deamination of adenosine monophos- tions may also lead to ammonia toxicity. Hyperammonemia phate and amino acid catabolism. In the brain, the latter refers to a clinical condition associated with elevated processes plus the activity of glutamate dehydrogenase ammonia levels manifested by a variety of symptoms and mediate ammonia production. After formation of ammonium signs, including significant central nervous system (CNS) from glutamine, α-ketoglutarate, a byproduct, may be abnormalities. Appropriate and timely management requires a degraded to produce two molecules of bicarbonate, which solid understanding of the fundamental pathophysiology, are then available to buffer acids produced by dietary sources. differential diagnosis, and treatment approaches available.
    [Show full text]
  • Second-Tier DNA Confirmation of Newborn Screening Results
    Second-tier DNA Confirmation of Newborn Screening by Targeted Next Generation Sequencing Edwin Naylor, Ph.D. MPH Andy Bhattacharjee , Ph.D. Erik Puffenberger, Ph.D.; Kevin Strauss, MD; Holmes Morton, MD Newborn Screening & Clinical Genomics 1961 1990’s 2010-2012 2 Robert Guthrie Development of develops simple automated MS/MS Newborn Screening screening across (NBS) several disorders Current de facto standard 2 Why Newborn Genomics? • Mendelian Diseases disproportionately affect Newborns - ~3500 genetic diseases with molecular basis - >10% of NICU admissions are genetic Clinical manifestation of Genetic diseases - Current NBS tests limited to 29+ diseases CHROMOSOMAL - 2nd tier DNA testing to validate biochemical results MULTI-FACTORIAL SINGLE GENE (MENDELIAN) • Advantage of NGS based DNA testing individuals # of Affected - Find causal variants (rare/novel) in gene(s) - A ‘universal’ NGS approach avoids repeated, serial BIRTH PUBERTY ADULT single gene testing Gelehrter TD, Collins FS, Ginsburg D. Principles of - Current Sanger sequencing is expensive ($3-10K) and Medical Genetics. 2nd ed. Baltimore, MD: Williams & slow (3 months to 1 year) Wilkins; 1998:1-42 NICU- Neonatal Intensive Care Unit NBS-Newborn Screening 3 NGS-Next Generation Sequencing Why Targeted (Exome) Sequencing for now? NGS Sequencing * Genomic DNA from Causal Mutations in Affected Individuals Exons/Target Regions Fold Test Menu Cost ($) Throughput Efficiency Whole Genome (Res.) 7,666* 1 1 Exome (Res) 1,200 15 95 Neonate Panel (Clinical) <1000 150 >1140 •Majority of known disease-causing mutations in exons •Exome = protein-encoding parts of genes •Targeted NGS is Cost & Throughput Efficient *Saunders et al., (2012) Rapid Whole Genome Sequencing for Genetic Disease Diagnosis in NICUs 4 Workflow for 2nd Tier Newborn Screening Sample 2h DNA Capture 92h Raw Data 10h Analysis 1h+ Isolation & Sequencing Management & Interpretation 8 samples, 105 Hrs, <$10,000 = Real Neonatal Genomics! 5 Workflow for 2nd Tier Newborn Screening Sample •High M.Wt.
    [Show full text]
  • Newborn Screening Laboratory Manual of Services
    Newborn Screening Laboratory Manual of Services Test Panel: Please see the following links for a detailed description of testing in the Newborn Screening section. Information about the Newborn Screening program is available here. Endocrine Disorders Congenital adrenal hyperplasia (CAH) Congenital hypothyroidism (TSH) Hemoglobinopathies Sickle cell disease (FS) Alpha (Barts) Sickle βeta Thalassemia (FSA) Other sickling hemoglobinopathies such as: FAS FAC FAD FAE Homozygous conditions such as: FC FD FE Metabolic Disorders Biotinidase deficiency Galactosemia Cystic fibrosis (CF) first tier screening for elevated immunoreactive trypsinogen (IRT) Cystic fibrosis second tier genetic mutation analysis on the top 4% IRT concentrations. Current alleles detected : F508del, I507del, G542X, G85E, R117H, 621+1G->T, 711+1G->T, R334W, R347P, A455E, 1717-1G->A, R560T, R553X, G551D, 1898+1G->A, 2184delA, 2789+5G->A, 3120+1G->A, R1162X, 3659delC, 3849+10kbC->T, W1282X, N1303K, IVS polyT T5/T7/T9 *Currently validating a mutation panel that includes the above alleles in addition to the following: 1078delT, Y122X, 394delTT, R347H, M1101K, S1255X, 1898+5G->T, 2183AA->G, 2307insA, Y1092X, 3876delA, 3905insT, S549N, S549R_1645A->C, S549R-1647T->G, S549R-1647T->G, V520F, A559T, 1677delTA, 2055del9->A, 2143delT, 3199del6, 406-1G->A, 935delA, D1152H, CFTRdele2, E60X, G178R, G330X, K710X, L206W, Q493X, Q890X, R1066C, R1158X, R75X, S1196X, W1089X, G1244E, G1349D, G551S, R560KT, S1251N, S1255P Amino acid disorders Phenylketonuria (PKU) / Hyperphenylalaninemia Maple
    [Show full text]
  • Disorders Included in the Newborn Screening Panel Disorders
    Disorders Included in the Newborn Screening Panel Disorders Detected by Tandem Mass Spectrometry Acylcarnitine Profile Amino Acid Profile Fatty Acid Oxidation Disorders Amino Acid Disorders Carnitine/Acylcarnitine Translocase Deficiency Argininemia 1 Carnitine Palmitoyl Transferase Deficiency Type I Argininosuccinic Aciduria 1 3-Hydroxy Long Chain Acyl-CoA Dehydrogenase 5-Oxoprolinuria 1 Deficiency Carbamoylphosphate Synthetase Deficiency 1 2,4-Dienoyl-CoA Reductase Deficiency Citrullinemia Medium Chain Acyl-CoA Dehydrogenase Deficiency Homocystinuria Multiple Acyl-CoA Dehydrogenase Deficiency Hypermethioninemia Neonatal Carnitine Palmitoyl Transferase Deficiency Hyperammonemia, Hyperornithinemia, Homocitrullinuria Type II Syndrome1 1 Short Chain Acyl-CoA Dehydrogenase Deficiency Hyperornithinemia with Gyral Atrophy Short Chain Hydroxy Acyl-CoA Dehydrogenase Maple Syrup Urine Disease Deficiency Phenylketonuria Trifunctional Protein Deficiency Classical/Hyperphenylalaninemia Very Long Chain Acyl-CoA Dehydrogenase Deficiency Biopterin Cofactor Deficiencies Tyrosinemia Organic Acid Disorders Transient Neonatal Tyrosinemia 2 Tyrosinemia Type I 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency Tyrosinemia Type II Glutaric Acidemia Type I Tyrosinemia Type III Isobutyryl-CoA Dehydrogenase Deficiency Isovaleric Acidemia 2-Methylbutyryl-CoA Dehydrogenase Deficiency 3-Methylcrotonyl-CoA Carboxylase Deficiency Other Observations 3-Methylglutaconyl-CoA Hydratase Deficiency Methylmalonic Acidemias Hyperalimentation Methylmalonyl-CoA Mutase Deficiency
    [Show full text]
  • On the Active Site Thiol of Y-Glutamylcysteine Synthetase
    Proc. Natl. Acad. Sci. USA Vol. 85, pp. 2464-2468, April 1988 Biochemistry On the active site thiol of y-glutamylcysteine synthetase: Relationships to catalysis, inhibition, and regulation (glutathione/cystamine/Escherichia coli/kidney/enzyme inactivation) CHIN-SHIou HUANG, WILLIAM R. MOORE, AND ALTON MEISTER Cornell University Medical College, Department of Biochemistry, 1300 York Avenue, New York, NY 10021 Contributed by Alton Meister, December 4, 1987 ABSTRACT y-Glutamylcysteine synthetase (glutamate- dithiothreitol, suggesting that cystamine forms a mixed cysteine ligase; EC 6.3.2.2) was isolated from an Escherichia disulfide between cysteamine and an enzyme thiol (15). coli strain enriched in the gene for this enzyme by recombinant Inactivation of the enzyme by the L- and D-isomers of DNA techniques. The purified enzyme has a specific activity of 3-amino-1-chloro-2-pentanone, as well as that by cystamine, 1860 units/mg and a molecular weight of 56,000. Comparison is prevented by L-glutamate (14). Treatment of the enzyme of the E. coli enzyme with the well-characterized rat kidney with cystamine prevents its interaction with the sulfoxi- enzyme showed that these enzymes have similar catalytic prop- mines. Titration of the enzyme with 5,5'-dithiobis(2- erties (apparent Km values, substrate specificities, turnover nitrobenzoate) reveals that the enzyme has a single exposed numbers). Both enzymes are feedback-inhibited by glutathione thiol that reacts with this reagent without affecting activity but not by y-glutamyl-a-aminobutyrylglycine; the data indicate (16). 5,5'-Dithiobis(2-nitrobenzoate) does not interact with that glutathione binds not only at the glutamate binding site but the thiol that reacts with cystamine.
    [Show full text]
  • EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies
    Focusing on Personalised Medicine EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies Extended carrier screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases, parents aren’t aware they are carriers and have no family history due to the rarity of some diseases in the general population. What is covered by the screening? Genomics For Life offers a comprehensive Extended Carrier Screening test, providing prospective parents with the information they require when planning their pregnancy. Extended Carrier Screening has been shown to detect carriers who would not have been considered candidates for traditional risk- based screening. With a simple mouth swab collection, we are able to test for over 419 genes associated with inherited diseases, including Fragile X Syndrome, Cystic Fibrosis and Spinal Muscular Atrophy. The assay has been developed in conjunction with clinical molecular geneticists, and includes genes listed in the NIH Genetic Test Registry. For a list of genes and disorders covered, please see the reverse of this brochure. If your gene of interest is not covered on our Extended Carrier Screening panel, please contact our friendly team to assist you in finding a gene test panel that suits your needs. Why have Extended Carrier Screening? Extended Carrier Screening prior to pregnancy enables couples to learn about their reproductive risk and consider a complete range of reproductive options, including whether or not to become pregnant, whether to use advanced reproductive technologies, such as preimplantation genetic diagnosis, or to use donor gametes.
    [Show full text]
  • Clinical Issues in Neonatal Care
    Linda Ikuta , MN, RN, CCNS, PHN , and Ksenia Zukowsky, PhD, APRN, NNP-BC ❍ Section Editors Clinical Issues in Neonatal Care 2.5 HOURS Continuing Education Deconstructing Black Swans An Introductory Approach to Inherited Metabolic Disorders in the Neonate Nicholas Ah Mew , MD ; Sarah Viall , MSN, PPCNP ; Brian Kirmse , MD ; Kimberly A. Chapman , MD, PhD ABSTRACT Background: Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. Purpose: This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. Methods/Search Strategy: An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Findings/Results: Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. Implications for Practice: When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Implications for Research: Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve. Key Words:
    [Show full text]
  • Mutation of the Fumarase Gene in Two Siblings with Progressive Encephalopathy and Fumarase Deficiency T
    Mutation of the Fumarase Gene in Two Siblings with Progressive Encephalopathy and Fumarase Deficiency T. Bourgeron,* D. Chretien,* J. Poggi-Bach, S. Doonan,' D. Rabier,* P. Letouze,I A. Munnich,* A. R6tig,* P. Landneu,* and P. Rustin* *Unite de Recherches sur les Handicaps Genetiques de l'Enfant, INSERM U393, Departement de Pediatrie et Departement de Biochimie, H6pital des Enfants-Malades, 149, rue de Sevres, 75743 Paris Cedex 15, France; tDepartement de Pediatrie, Service de Neurologie et Laboratoire de Biochimie, Hopital du Kremlin-Bicetre, France; IFaculty ofScience, University ofEast-London, UK; and IService de Pediatrie, Hopital de Dreux, France Abstract chondrial enzyme (7). Human tissue fumarase is almost We report an inborn error of the tricarboxylic acid cycle, fu- equally distributed between the mitochondria, where the en- marase deficiency, in two siblings born to first cousin parents. zyme catalyzes the reversible hydration of fumarate to malate They presented with progressive encephalopathy, dystonia, as a part ofthe tricarboxylic acid cycle, and the cytosol, where it leucopenia, and neutropenia. Elevation oflactate in the cerebro- is involved in the metabolism of the fumarate released by the spinal fluid and high fumarate excretion in the urine led us to urea cycle. The two isoenzymes have quite homologous struc- investigate the activities of the respiratory chain and of the tures. In rat liver, they differ only by the acetylation of the Krebs cycle, and to finally identify fumarase deficiency in these NH2-terminal amino acid of the cytosolic form (8). In all spe- two children. The deficiency was profound and present in all cies investigated so far, the two isoenzymes have been found to tissues investigated, affecting the cytosolic and the mitochon- be encoded by a single gene (9,10).
    [Show full text]
  • Inherited Metabolic Disease
    Inherited metabolic disease Dr Neil W Hopper SRH Areas for discussion • Introduction to IEMs • Presentation • Initial treatment and investigation of IEMs • Hypoglycaemia • Hyperammonaemia • Other presentations • Management of intercurrent illness • Chronic management Inherited Metabolic Diseases • Result from a block to an essential pathway in the body's metabolism. • Huge number of conditions • All rare – very rare (except for one – 1:500) • Presentation can be non-specific so index of suspicion important • Mostly AR inheritance – ask about consanguinity Incidence (W. Midlands) • Amino acid disorders (excluding phenylketonuria) — 18.7 per 100,000 • Phenylketonuria — 8.1 per 100,000 • Organic acidemias — 12.6 per 100,000 • Urea cycle diseases — 4.5 per 100,000 • Glycogen storage diseases — 6.8 per 100,000 • Lysosomal storage diseases — 19.3 per 100,000 • Peroxisomal disorders — 7.4 per 100,000 • Mitochondrial diseases — 20.3 per 100,000 Pathophysiological classification • Disorders that result in toxic accumulation – Disorders of protein metabolism (eg, amino acidopathies, organic acidopathies, urea cycle defects) – Disorders of carbohydrate intolerance – Lysosomal storage disorders • Disorders of energy production, utilization – Fatty acid oxidation defects – Disorders of carbohydrate utilization, production (ie, glycogen storage disorders, disorders of gluconeogenesis and glycogenolysis) – Mitochondrial disorders – Peroxisomal disorders IMD presentations • ? IMD presentations • Screening – MCAD, PKU • Progressive unexplained neonatal
    [Show full text]
  • Amino Acid Disorders 105
    AMINO ACID DISORDERS 105 Massaro, A. S. (1995). Trypanosomiasis. In Guide to Clinical tions in biological fluids relatively easy. These Neurology (J. P. Mohrand and J. C. Gautier, Eds.), pp. 663– analyzers separate amino acids either by ion-ex- 667. Churchill Livingstone, New York. Nussenzweig, V., Sonntag, R., Biancalana, A., et al. (1953). Ac¸a˜o change chromatography or by high-pressure liquid de corantes tri-fenil-metaˆnicos sobre o Trypanosoma cruzi in chromatography. The results are plotted as a graph vitro: Emprego da violeta de genciana na profilaxia da (Fig. 1). The concentration of each amino acid can transmissa˜o da mole´stia de chagas por transfusa˜o de sangue. then be calculated from the size of the corresponding O Hospital (Rio de Janeiro) 44, 731–744. peak on the graph. Pagano, M. A., Segura, M. J., DiLorenzo, G. A., et al. (1999). Cerebral tumor-like American trypanosomiasis in Most amino acid disorders can be diagnosed by acquired immunodeficiency syndrome. Ann. Neurol. 45, measuring the concentrations of amino acids in 403–406. blood plasma; however, some disorders of amino Rassi, A., Trancesi, J., and Tranchesi, B. (1982). Doenc¸ade acid transport are more easily recognized through the Chagas. In Doenc¸as Infecciosas e Parasita´rias (R. Veroesi, Ed.), analysis of urine amino acids. Therefore, screening 7th ed., pp. 674–712. Guanabara Koogan, Sa˜o Paulo, Brazil. Spina-Franc¸a, A., and Mattosinho-Franc¸a, L. C. (1988). for amino acid disorders is best done using both South American trypanosomiasis (Chagas’ disease). In blood and urine specimens. Occasionally, analysis of Handbook of Clinical Neurology (P.
    [Show full text]
  • Genes Investigated
    BabyNEXTTM EXTENDED Investigated genes and associated diseases Gene Disease OMIM OMIM Condition RUSP gene Disease ABCC8 Familial hyperinsulinism 600509 256450 Metabolic disorder - ABCC8-related Inborn error of amino acid metabolism ABCD1 Adrenoleukodystrophy 300371 300100 Miscellaneous RUSP multisystem (C) * diseases ABCD4 Methylmalonic aciduria and 603214 614857 Metabolic disorder - homocystinuria, cblJ type Inborn error of amino acid metabolism ACAD8 Isobutyryl-CoA 604773 611283 Metabolic Disorder - RUSP dehydrogenase deficiency Inborn error of (S) ** organic acid metabolism ACAD9 acyl-CoA dehydrogenase-9 611103 611126 Metabolic Disorder - (ACAD9) deficiency Inborn error of fatty acid metabolism ACADM Acyl-CoA dehydrogenase, 607008 201450 Metabolic Disorder - RUSP medium chain, deficiency of Inborn error of fatty (C) acid metabolism ACADS Acyl-CoA dehydrogenase, 606885 201470 Metabolic Disorder - RUSP short-chain, deficiency of Inborn error of fatty (S) acid metabolism ACADSB 2-methylbutyrylglycinuria 600301 610006 Metabolic Disorder - RUSP Inborn error of (S) organic acid metabolism ACADVL very long-chain acyl-CoA 609575 201475 Metabolic Disorder - RUSP dehydrogenase deficiency Inborn error of fatty (C) acid metabolism ACAT1 Alpha-methylacetoacetic 607809 203750 Metabolic Disorder - RUSP aciduria Inborn error of (C) organic acid metabolism ACSF3 Combined malonic and 614245 614265 Metabolic Disorder - methylmalonic aciduria Inborn error of organic acid metabolism 1 ADA Severe combined 608958 102700 Primary RUSP immunodeficiency due
    [Show full text]